Risk Of Acute Cardiovascular Events Research Articles

Physical, Psychological and Chemical Triggers of Acute Cardiovascular Events

In addition to the impact of long-term stressors such as sedentary lifestyle and long-term exposure to high levels of air pollution, many studies have shown that there is an increased risk of acute cardiovascular events immediately after behavioral, psychosocial, and environmental triggers.1–8 After the landmark study documenting the increased rates of myocardial infarction (MI) related to the 1981 earthquake in Athens9 and the description of the circadian variation in the incidence of MI by Muller et al,10 various studies documented the frequency of potential triggers in the period immediately preceding MI onset. Although the observational studies examining physical, psychological, and chemical triggers of acute cardiovascular events are not without limitations, studies continue to show that short-term exposures appear to play a role in the occurrence of cardiovascular events. These triggers have been discussed in previous reviews,1–8 with a general consensus that different preventive strategies may be appropriate for particular triggers. The purpose of this review is to bring together the evidence of the association between several triggers and cardiovascular outcomes and to discuss the common underlying pathophysiology of these triggers. Rather than leading to slowly progressive atherosclerosis, triggers represent the final step in the pathophysiological process leading to cardiovascular outcomes among susceptible individuals, such as those with vulnerable atherosclerotic plaque, chronic atherosclerotic disease, disorders of the cardiac conduction system, and microvascular disease. In the presence of a vulnerable atherosclerotic plaque, chemical, physical, and psychological stressors may trigger transient vasoconstrictive and prothrombotic effects that ultimately cause plaque disruption and thrombosis. Even in the absence of an occlusive thrombus, triggers may lower the threshold for cardiac electric instability and increase cardiac sympathetic activation via centrally mediated release of catecholamines, thereby evoking primary ventricular fibrillation and sudden cardiac death.11 Figure 1 depicts several potential …

Secondhand Smoke Exposure and Coronary Artery Calcification among Nonsmoking Participants of a Population-Based Cohort

Background: Secondhand smoke (SHS) consists of fine particulate matter, carcinogens, and various toxins that affect large parts of the population. SHS increases the risk for acute cardiovascular events and may contribute to the development of atherosclerosis.Objectives: We investigated the association of SHS with coronary artery calcification (CAC).Methods: In this cross-sectional analysis, we used baseline data (2000–2003) from 1,766 never-smokers without clinically manifested coronary heart disease, 45–75 years of age, from the Heinz Nixdorf Recall Study, an ongoing, prospective, population-based cohort study in Germany. Self-reported frequent SHS at home, at work, and in other places was assessed by questionnaire. CAC scores were derived based on electron-beam computed tomography. We conducted multiple linear regression analysis using exposure to SHS as the explanatory variable and ln(CAC+1) as the response variable. We conducted logistic regression to estimate the odds ratio (OR) for presence of any CAC.Results: Frequent exposure to SHS was reported by 21.5% of participants. After adjustment for age, sex, and socioeconomic status, CAC + 1 was 21.1% [95% confidence interval (CI): –5.5%, 55.2%] higher in exposed than in unexposed participants. After adjusting for other cardiovascular risk factors, the association was attenuated (15.4%; 95% CI: –9.6%, 47.2%). SHS exposure was also associated with a CAC score > 0 (fully adjusted OR = 1.38; 95% CI: 1.03, 1.84).Conclusions: Self-reported frequent exposure to SHS was associated with subclinical coronary atherosclerosis in our cross-sectional study population. Considering the widespread exposure and the clinical relevance of coronary atherosclerosis, this result, if confirmed, is of public health importance.

Outcomes in patients with chest pain evaluated in a chest pain unit: The Chest Pain Evaluation in the Emergency Room study cohort

Limited data exist on the long-term outcomes of patients who undergo evaluation in a chest pain unit (CPU). Our study included patients with chest pain at intermediate risk for acute cardiovascular events enrolled in the CHEER study. The primary outcome included a composite of death, myocardial infarction, acute heart failure, stroke, and out-of-hospital cardiac arrest. The secondary outcome included a composite of cardiovascular death, myocardial infarction, acute heart failure, stroke, revascularization, and unstable angina. Data were obtained through a medical record review. We compared outcomes between groups randomized to the CPU versus admission, those admitted from the CPU versus dismissed home, and those who were admitted versus dismissed home after a cardiac stress test in the emergency department. The final analysis included 407 patients. Median surveillance length was 5.5 years. No differences in the primary outcome or secondary outcome existed between patients randomized to the CPU versus admitted to hospital (21.6% vs 20.2% and 29.9% vs 33.0%, respectively, P > .05 for all comparisons). Patients admitted from the CPU had higher rates of the secondary outcome (adjusted hazard ratio 2.26) than patients dismissed from the CPU. Patients admitted after a cardiac stress test in the CPU had higher rates of the secondary outcome (adjusted hazard ratio 2.42) than patients dismissed from the CPU. A CPU does not increase long-term adverse outcomes in patients with chest pain at intermediate risk for an acute event.

Evidence Linking Hypoglycemic Events to an Increased Risk of Acute Cardiovascular Events in Patients With Type 2 Diabetes

OBJECTIVEThis retrospective study examined the association between ICD-9-CM–coded outpatient hypoglycemic events (HEs) and acute cardiovascular events (ACVEs), i.e., acute myocardial infarction, coronary artery bypass grafting, revascularization, percutaneous coronary intervention, and incident unstable angina, in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSData were derived from healthcare claims for individuals with employer-sponsored primary or Medicare supplemental insurance. A baseline period (30 September 2006 to 30 September 2007) was used to identify eligible patients and collect information on their clinical and demographic characteristics. An evaluation period (1 October 2007 to 30 September 2008) was used to identify HEs and ACVEs. Patients aged ≥18 years with type 2 diabetes were selected for analysis by a modified Healthcare Effectiveness Data and Information Set algorithm. Data were analyzed with multiple logistic regression and backward stepwise selection (maximum P = 0.01) with adjustment for important confounding variables, including age, sex, geography, insurance type, comorbidity scores, cardiovascular risk factors, diabetes complications, total baseline medical expenditures, and prior ACVEs.RESULTSOf the 860,845 patients in the analysis set, 27,065 (3.1%) had ICD-9-CM–coded HEs during the evaluation period. The main model retained 17 significant independent variables. Patients with HEs had 79% higher regression-adjusted odds (HE odds ratio [OR] 1.79; 95% CI 1.69–1.89) of ACVEs than patients without HEs; results in patients aged ≥65 years were similar to those for the entire population (HE OR 1.78, 95% CI 1.65–1.92).CONCLUSIONSICD-9-CM–coded HEs were independently associated with an increased risk of ACVEs. Further studies of the relationship between hypoglycemia and the risk of ACVEs are warranted.

Myocardial infarction vaccine? Evidence supporting the influenza vaccine for secondary prevention

This editorial refers to ‘Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome’, by A. Phrommintikul et al. doi:10.1093/eurheartj/ehr004 Coronary heart disease (CHD) is one of the leading causes of morbidity and mortality worldwide. Both primary and secondary prevention strategies thus far substantially reduce the risk of acute cardiovascular events, but still a substantial number of patients have outcomes. As a result, there has been a call for newer avenues for risk reduction. The complex interplay between infection and atherosclerosis has been under scientific scrutiny for years. Many organisms have been implicated, including herpesviruses, Chlamydia pneumoniae , Mycoplasma pneumoniae , periodontal pathogens, and many others.1 There was much excitement regarding C. pneumoniae given its association with CHD and animal models suggesting a direct involvement in the pathogenesis of atherosclerosis, but trials using suppressive antibiotic therapy failed to show a reduction in clinical events.2,3 Although the evidence for chronic infections of intracellular pathogens and atherosclerosis exists, it was speculated that infection in CHD had begun the process of atherosclerosis decades before, thereby limiting the ability to employ antibiotic treatment so late in the evolution of CHD. However, the paradigm of inflammation significantly contributing to atherosclerosis and triggering acute cardiovascular events is firmly established, and as such there has been a continued interest in the role of infection as a contributor to this inflammatory response. Of acute infectious organisms, the influence of the influenza virus has been closely examined since it is one of the most severe respiratory viral pathogens and essentially the only one with …

Secondhand Smoke Exposure and Coronary Artery Calcification Among Nonsmoking Adults

PP-31-002 Background/Aims: Exposure to secondhand smoke (SHS) is an exposure to air pollution of fine particulate matter, carcinogens, and various toxins, affecting large parts of the population. SHS increases the risk for acute cardiovascular events and may contribute to the development of atherosclerosis. We investigate the association of SHS with coronary artery calcification (CAC). Methods: In the present cross-sectional analysis, we used baseline data (2000–2003) of 1891 never smokers, aged 45–75 years, from an ongoing, prospective, population-based cohort study in Germany. Frequent SHS at home, at work, and in other places was assessed by questionnaire. CAC was measured by electron-beam computed tomography. We conducted multiple linear regression analysis using exposure to SHS (any location) as the explanatory variable and ln(CAC+1) as the response variable, adjusting for gender, age, socioeconomic status, and cardiovascular risk factors. Results: Frequent exposure to SHS was reported by 21.7% of respondents. After adjustment for age, gender, and socioeconomic status, (CAC+1) was 25.9% (95% confidence interval [CI]: −1.0% to 60.2%) higher in the exposed than in the unexposed. Inclusion of further cardiovascular risk factors (diabetes, cholesterol, body mass index, physical activity) reduced the estimate (19.7%; 95% CI: −5.4% to 51.5%). Highest effects were seen for exposure at home (35.8%; 95% CI: −2.8% to 89.8%). The effect of SHS was comparable to up to 3 years of older vascular age, depending on age range and sex. Conclusion: Our study provides first suggestive evidence of an association between exposure to SHS and coronary atherosclerosis. Considering the widespread exposure and the clinical relevance of coronary atherosclerosis, this result, if confirmed, is likely to be of high public health importance.

Acetaminophen Increases Blood Pressure in Patients With Coronary Artery Disease

Because traditional nonsteroidal antiinflammatory drugs are associated with increased risk for acute cardiovascular events, current guidelines recommend acetaminophen as the first-line analgesic of choice on the assumption of its greater cardiovascular safety. Data from randomized clinical trials prospectively addressing cardiovascular safety of acetaminophen, however, are still lacking, particularly in patients at increased cardiovascular risk. Hence, the aim of this study was to evaluate the safety of acetaminophen in patients with coronary artery disease. The 33 patients with coronary artery disease included in this randomized, double-blind, placebo-controlled, crossover study received acetaminophen (1 g TID) on top of standard cardiovascular therapy for 2 weeks. Ambulatory blood pressure, heart rate, endothelium-dependent and -independent vasodilatation, platelet function, endothelial progenitor cells, markers of the renin-angiotensin system, inflammation, and oxidative stress were determined at baseline and after each treatment period. Treatment with acetaminophen resulted in a significant increase in mean systolic (from 122.4±11.9 to 125.3±12.0 mm Hg P=0.02 versus placebo) and diastolic (from 73.2±6.9 to 75.4±7.9 mm Hg P=0.02 versus placebo) ambulatory blood pressures. On the other hand, heart rate, endothelial function, early endothelial progenitor cells, and platelet function did not change. This study demonstrates for the first time that acetaminophen induces a significant increase in ambulatory blood pressure in patients with coronary artery disease. Thus, the use of acetaminophen should be evaluated as rigorously as traditional nonsteroidal antiinflammatory drugs and cyclooxygenase-2 inhibitors, particularly in patients at increased cardiovascular risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00534651.

Systemic and Intraplaque Mediators of Inflammation Are Increased in Patients Symptomatic for Ischemic Stroke

The concept of "vulnerable plaque" has been extended to the more recent definition of the "cardiovascular vulnerable patient," in which "intraplaque" and "systemic" factors contribute to the cumulative risk of acute cardiovascular events. Thus, we investigated the possible role of systemic and intraplaque inflammation in patients asymptomatic versus symptomatic for ischemic stroke. Regions upstream and downstream the blood flow were isolated from internal carotid plaques of patients asymptomatic (n=63) or symptomatic (n=18) for ischemic stroke. Specimens were analyzed for lipid, collagen, macrophage, lymphocyte, neutrophil, mast cell and smooth muscle cell content, and chemokine and cytokine mRNA expression. Chemokine receptors and adhesion molecules were assessed on circulating leukocytes by flow cytometry. Systemic inflammatory markers and biochemical parameters were measured on total blood, plasma, and serum. Tumor necrosis factor-alpha and CCL5 serum levels as well as intercellular adhesion molecule-1 expression on circulating neutrophils were increased in symptomatic as compared with asymptomatic patients. Collagen content and smooth muscle cell infiltration were decreased in symptomatic plaques. In upstream regions of symptomatic plaques, lipid content and lymphocyte infiltration were increased. In downstream regions of symptomatic plaques, macrophage, neutrophil, and mast cell infiltration were increased. Intraplaque collagen content was positively correlated with smooth muscle cell infiltration and inversely correlated with macrophages, neutrophils, or serum tumor necrosis factor-alpha. Collagen reduction in downstream regions and serum tumor necrosis factor-alpha were independently associated with the likelihood of being symptomatic. Inflammatory mediators are increased in ischemic stroke. Despite statistically significant, the correlation between tumor necrosis factor-alpha serum level and intraplaque vulnerability was weak and probably of limited biological importance.

Plaque characteristics of nonobstructive coronary lesions in diabetic patients: an intravascular ultrasound virtual histology analysis

Patients with diabetes mellitus are known to be at increased risk for acute cardiovascular events. We used intravascular ultrasound virtual histology (IVUS-VH) to examine whether nonobstructive coronary artery lesions of diabetic patients have distinct plaque composition and morphology compared with nondiabetic patients. A total of 41 patients (13 diabetic and 28 nondiabetic) with proximally located angiographically nonobstructive coronary lesions were prospectively enrolled. In addition to plaque geometry, IVUS-VH lesion evaluation of the fibrous, fibro-fatty, necrotic core and calcified plaque components was performed. An IVUS-derived thin-cap fibroatheroma (IDTCFA) was defined as a lesion with a confluent necrotic core of at least 10% lumen cross-sectional area without evident overlying fibrous tissue and a plaque atheroma volume of at least 40% in at least three consecutive frames. Coronary artery lesions of diabetic and nondiabetic patients had similar plaque geometry. Lesions of diabetic patients were more likely to be positively remodeled than those of nondiabetic patients (67 vs. 27%, respectively, P = 0.02). Plaques of diabetic patients had significantly higher necrotic core percentages (23.3 +/- 6.1 vs. 17.1 +/- 8.7%, P = 0.03) and lower fibro-fatty tissue percentages (8 +/- 5 vs. 14.2 +/- 7.5%, P = 0.01) than those of nondiabetic patients. In addition, IDTCFAs were significantly more prevalent at the minimal lumen area site of diabetic patients compared to nondiabetic patients (92 vs. 54%, respectively, P = 0.02). After adjustment for various confounders, diabetes mellitus remained as the only independent clinical predictor of IDTCFAs at the minimal lumen area site [odds ratio (OR) 9.43, 95% confidence interval (CI) 1.06-84.04, P = 0.04]. Nonobstructive coronary artery lesions of diabetic patients have distinct compositional and morphological features, suggesting that these differences may explain the increased likelihood of coronary events in diabetic patients.

It is just a game: lack of association between watching football matches and the risk of acute cardiovascular events

The role of trigger factors in acute cardiovascular events has been much studied in the past few years. A recent study analysed changes in the rates of cardiac emergencies in Bavaria (Germany) during the last Football World Cup. The authors reported a 2.7-fold increase in the incidence of cardiac emergencies in the 12 h before and after football matches involving the German team, which sparked the debate on the necessity of the introduction of ad hoc cardiovascular preventive measures. We studied 25,159 hospital admissions for acute myocardial infarction (AMI) among the Italian population during three international football competitions: the World Cup 2002, the European Championship 2004 and the World Cup 2006. Poisson regression was used to estimate the relative risk of hospital admission for AMI on the days when football matches involving the Italian team were disputed, compared with the other days of the three competitions. Furthermore, we reviewed the available published studies regarding the association between football matches and the risk of cardiovascular events. We did not find an increase in the rates of admission for AMI on the days of football matches involving Italy in either the single competitions or the three competitions combined (relative risk 1.01; 95% confidence interval 0.98-1.05). We identified 10 studies published on this topic. With the exception of the recently published German study and two small Swiss studies, all relative risk estimates were between 0.7 and 1.3. The cardiovascular effects of watching football matches are likely to be, if anything, very small.

Adherence to Antihypertensive Medications and Cardiovascular Morbidity Among Newly Diagnosed Hypertensive Patients

Nonadherence to antihypertensive treatment is a common problem in cardiovascular prevention and may influence prognosis. We explored predictors of adherence to antihypertensive treatment and the association of adherence with acute cardiovascular events. Using data obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database, we selected 18,806 newly diagnosed hypertensive patients >or=35 years of age during the years 2000 to 2001. Subjects included were newly treated for hypertension and initially free of cardiovascular diseases. Patient adherence was subdivided a priori into 3 categories-high (proportion of days covered, >or=80%), intermediate (proportion of days covered, 40% to 79%), and low (proportion of days covered, <or=40%)-and compared with the long-term occurrence of acute cardiovascular events through the use of multivariable models adjusted for demographic factors, comorbidities, and concomitant drug use. At baseline (ie, 6 months after index diagnosis), 8.1%, 40.5%, and 51.4% of patients were classified as having high, intermediate, and low adherence levels, respectively. Multiple drug treatment (odds ratio, 1.62; 95% CI, 1.43 to 1.83), dyslipidemia (odds ratio, 1.52; 95% CI, 1.24 to 1.87), diabetes mellitus (odds ratio, 1.40; 95% CI, 1.15 to 1.71), obesity (odds ratio, 1.50; 95% CI, 1.26 to 1.78), and antihypertensive combination therapy (odds ratio, 1.29; 95% CI, 1.15 to 1.45) were significantly (P<0.001) associated with high adherence to antihypertensive treatment. Compared with their low-adherence counterparts, only high adherers reported a significantly decreased risk of acute cardiovascular events (hazard ratio, 0.62; 95% CI, 0.40 to 0.96; P=0.032). The long-term reduction of acute cardiovascular events associated with high adherence to antihypertensive treatment underscores its importance in assessments of the beneficial effects of evidence-based therapies in the population. An effort focused on early antihypertensive treatment initiation and adherence is likely to provide major benefits.

IA 008 Coronary Angiography by Multidetector Computed Tomography Predicts Clinically Driven Revascularization in Suspected Acute Coronary Syndrome Better than in Chronic Stable Coronary Artery Disease

Inflammation constitutes a complex, highly conserved cascade of molecular and cellular events. Inflammation has been labeled as “the fire within,” is highly regulated, and is critical to host defense and tissue repair. In general, inflammation is beneficial and has evolved to promote survival. However, inflammation can also be maladaptive when chronically activated and sustained, leading to progressive tissue injury and reduced survival. Examples of a maladaptive response include rheumatologic disease and atherosclerosis. Despite evidence gathered by Virchow over 100 years ago showing that inflammatory white cells play a role in atherogenesis, atherosclerosis was until recently viewed as a disease of passive cholesterol accumulation in the subendothelial space. This view has been supplanted by considerable basic scientific and clinical evidence demonstrating that every step of atherogenesis, from the development of endothelial cell dysfunction to foam cell formation, plaque formation and progression, and ultimately plaque rupture stemming from architectural instability, is driven by the cytokines, interleukins, and cellular constituents of the inflammatory response. Herein we provide an overview of the role of inflammation in atherosclerotic cardiovascular disease, discuss the predictive value of various biomarkers involved in inflammation, and summarize recent clinical trials that evaluated the capacity of various pharmacologic interventions to attenuate the intensity of inflammation and impact risk for acute cardiovascular events.

Thienopyridine therapy and risk for cardiovascular events in secondary prevention

Platelets are critical modulators of atherothrombotic events. In the acute setting, platelets are activated and aggregate on the surface of atherosclerotic plaque that has ruptured, fissured, or developed erosions. The overlying thrombus leads to sudden development of arterial luminal obstruction, inducing ischemia and cellular necrosis. Inhibiting platelet reactivity is an important therapeutic goal in patients at risk for acute cardiovascular events. The thienopyridines are potent inhibitors of platelet aggregation and block the binding of adenosine 5'-diphosphate to purinergic receptors on the surface of the platelet membrane. The thienopyridine class includes ticlopidine, clopidogrel, and prasugrel. Clopidogrel is the most intensively studied. In recent years it has become apparent that approximately 20% to 25% of patients who would be expected to benefit from clopidogrel therapy are resistant to this drug, largely due to a polymorphism in the gene for cytochrome P450 2C19. The efficacy of clopidogrel can also be reduced if patients are receiving concomitant therapy with a proton pump inhibitor such as omeprazole. Prasugrel is a third-generation thienopyridine with faster time to onset and greater consistency in inhibiting platelet activity, and it has shown superiority to clopidogrel for reducing cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary interventions.

C-Reactive Protein Elicits White Blood Cell Activation in Humans

Objective Consistent epidemiologic evidence suggests that acute infections increase the risk for acute cardiovascular events. We tested in humans whether activation of peripheral leukocytes in reaction to the administration of recombinant human C-reactive protein (rhCRP) may provide a mechanism for infectious diseases to promote atherosclerotic disease. Methods and Results By using quantitative real-time polymerase chain reaction analysis, whole-blood expression profiles were analyzed for 95 inflammatory markers before and after infusion of 1.25 mg/kg rhCRP in 5 male volunteers. Relevant transcript levels were measured at baseline and 4 and 8 hours after rhCRP-infusion. CRP caused significant up-regulation of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, plasminogen activator urokinase, macrophage inflammatory protein 1α, and nuclear factor of kappa B inhibitor mRNAs in peripheral leukocytes. mRNA up-regulation of MMP-9 and MCP-1 was 17- and 11-fold, respectively. The corresponding increase in plasma protein levels of MMP-9 (78 ± 32 ng/mL to 109 ± 41 ng/mL; P = .014) and MCP-1 (312 ± 92 pg/mL to 2590 ± 898 pg/mL; P = .007) closely mirrored mRNA findings. Also, in whole-blood culture stimulation assays, CRP induced proinflammatory changes. Notably, heat inactivation abolished the capacity of CRP to evoke these proinflammatory changes, excluding a role for contaminants within the purified CRP preparation. Conclusion CRP elicits activation of peripheral leukocytes with ensuing secretion of plaque-destabilizing mediators. These findings are consistent with the hypothesis that infectious diseases trigger manifestations of atherosclerosis, in which CRP elevation might contribute to the onset of cardiovascular events.

Air Pollution and Risk of Stroke

Epidemiologic studies linking ambient air pollution to the onset of acute cardiovascular events often rely on date of hospital admission for exposure assessment. We investigated the extent of exposure misclassification resulting from assigning exposure to particulate matter based on (1) date of hospital admission, or (2) time of hospital presentation compared with particulate matter exposure based on time of stroke symptom onset. We performed computer simulations to evaluate the impact of this source of exposure misclassification on estimates of air pollution health effects in the context of a time-stratified case-crossover study. Among 1101 patients admitted for a confirmed acute ischemic stroke to a Boston area hospital, symptom onset occurred a median of 1 calendar day before hospital admission (range = 0-30 days). The difference between ambient particulate matter exposure based on the calendar day of admission versus time of symptom onset ranged from -47 to 36 microg/m3 (-0.1 +/- 7.1 microg/m3; mean +/- SD). The simulation study indicated that for nonnull associations, exposure assessment based on hospitalization date led to estimates that were biased toward the null by 60%-66%, whereas assessment based on time of hospital presentation yielded estimates that were biased toward the null by 37%-42%. Epidemiologic studies of air pollution-related risk of acute cardiovascular events that assess exposure based on date of hospitalization likely underestimate the strength of associations. Using data on time of hospital presentation would marginally attenuate, but not eliminate, this important source of bias.

Drug therapy for hypertriglyceridemia: Fibrates and omega-3 fatty acids

The reduction of low-density lipoprotein cholesterol in patients at risk for acute cardiovascular events is the cornerstone of lipid management in both the primary and secondary prevention settings. Serum triglyceride levels exceeding 150 mg/dL are abnormal and confer increased risk for developing coronary artery disease in both men and women. Serum triglycerides are derived from both dietary and endogenous biosynthetic pathways. Triglyceride metabolism has a complex regulatory circuitry and intimately impacts the production and disposal of multiple lipoprotein species. Hypertriglyceridemia is highly prevalent and is associated with multiple forms of dyslipidemia but tends to be undertreated. Therapeutic intervention with fibric acid derivatives and omega-3 fish oils is associated with significant reductions in both fasting and postprandial serum triglyceride concentrations. A variety of prospective, placebo-controlled clinical trials have also shown that these agents significantly impact risk for multiple cardiovascular end points.

Phosphodiesterase type 5 inhibitors and endothelial function

Erectile dysfunction (ED) and endothelial dysfunction are common in individuals with multiple cardiovascular risk factors (CRFs) and are longitudinal predictors of cardiovascular events. ED is associated with systemic endothelial cell activation/dysfunction independent from CRFs or from diffuse, unrecognized vascular damage. The pathogenesis of endothelial dysfunction and ED is intimately linked through increased expression and activation of endothelial nitric oxide (NO) synthase and the subsequent physiologic actions of NO. Reduced biologic activity of endothelium-derived NO links human atherosclerosis to ED and underscores the role of altered endothelium in the pathogenesis of both conditions. ED may be the only clinical marker of systemic endothelial damage that is associated with a documented future risk of acute cardiovascular events. Searching for ED might be relevant in men with CRFs and no other clinical atherosclerosis in order to identify patients who could benefit from phosphodiesterase type 5 inhibitors to reduce their cardiovascular risk while treating ED.

High-Density Lipoprotein Metabolism: Potential Therapeutic Targets

It is well recognized that the lowering of low-density lipoprotein (LDL) cholesterol can substantially reduce coronary artery disease (CAD)-related morbidity and mortality. The prevention and management of CAD has chiefly focused on 1 component of the lipid profile: the reduction of LDL cholesterol. Yet, the majority of patients in both the primary and secondary prevention settings continue to experience significant residual risk for acute cardiovascular events even when their LDL cholesterol is lowered aggressively with combinations of lifestyle modification and pharmacologic intervention. As a result, there is increased focus on targeting and treating low serum levels of high-density lipoprotein (HDL) cholesterol in an effort to further reduce risk for cardiovascular events, including myocardial infarction, unstable angina, ischemic stroke, and death. Epidemiologically high serum levels of HDL cholesterol are associated with reduced risk for the development of atherosclerotic disease. HDL particles are believed to be antiatherogenic secondary to their capacity to drive reverse cholesterol transport and antagonize pathways of inflammation, thrombosis, and oxidation. HDL cholesterol can be quite challenging to raise in many individuals because of the large number of polymorphisms in the genes, enzymes, cell surface receptors, and apoproteins that regulate the serum concentrations, functionality, and patterns of metabolism of HDL particles This article reviews HDL metabolism and established as well as emerging therapeutic approaches to raising serum concentrations of this fascinating and complex lipoprotein.

Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se?

Introduction and hypothesisEpidemiological observations suggest links between osteoporosis and risk of acute cardiovascular events and vice versa. Whether the two clinical conditions are linked by common pathogenic factors or atherosclerosis per se remains incompletely understood. We investigated whether serum lipids and polymorphism in the ApoE gene modifying serum lipids could be a biological linkage.MethodsThis was an observational study including 1176 elderly women 60–85 years old. Women were genotyped for epsilon (ɛ) allelic variants of the ApoE gene, and data concerning serum lipids (total cholesterol, triglycerides, HDL-C, LDL-C, apoA1, ApoB, Lp(a)), hip and spine BMD, aorta calcification (AC), radiographic vertebral fracture and self-reported wrist and hip fractures, cardiovascular events together with a wide array of demographic and lifestyle characteristics were collected.ResultsPresence of the ApoE ɛ4 allele had a significant impact on serum lipid profile, yet no association with spine/hip BMD or AC could be established. In multiple regression models, apoA1 was a significant independent contributor to the variation in AC. However, none of the lipid components were independent contributors to the variation in spine or hip BMD. When comparing the women with or without vertebral fractures, serum triglycerides showed significant differences. This finding was however not applicable to hip or wrist fractures. After adjustment for age, severe AC score (≥6) and/or manifest cardiovascular disease increased the risk of hip but not vertebral or wrist fractures.ConclusionThe contribution of serum lipids to the modulators of BMD does not seem to be direct but rather indirect via promotion of atherosclerosis, which in turn can affect bone metabolism locally, especially when skeletal sites supplied by end-arteries are concerned. Further studies are needed to explore the genetic or environmental risk factors underlying the association of low triglyceride levels to vertebral fractures.

Influenza Vaccination and Risk of Incident Myocardial Infarction

Background: Several studies suggest that influenza vaccination may be associated with a decreased risk of acute cardiovascular events. We examined the association between influenza vaccination and risk of incident myocardial infarction (MI) in persons at least 65 years of age in a population-based case-control study.Methods: Case subjects were members of Group Health Cooperative (GHC), a health maintenance organization, with incident MI during 1992-1998. Control subjects were GHC members without a history of MI who were frequency matched to case subjects by age, sex, calendar year, and presence of treated hypertension. The medical records of 750 case subjects with MI and 1735 controls were reviewed.Results: Receipt of influenza vaccine was not associated with risk of incident MI during the months of November through March (odds ratio [OR]: 0.97, 95% confidence interval [CI]: 0.75-1.27) or April through September (OR: 0.97, 95% CI 0.75-1.26).Conclusions: This study does not provide evidence supporting an association of influenza vaccination and reduction in risk of myocardial infarction.The findings and conclusions in this paper are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.